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August 12, 2016
Scientist Studies Brain Damage from Excessive Alcohol Use

An evening of one drink too many can have dizzying effects. Some of the cognitive deficits from consuming too much alcohol—such as slower reaction times and impaired memory—can be especially profound among chronic, heavy alcohol users.

Dr. Marlene O. Berman
Dr. Marlene O. Berman

Dr. Marlene Oscar Berman has studied alcohol’s effects on the brain for more than 40 years. She started out studying memory impairments in rhesus monkeys while in graduate school. She then turned to brain damage in people. A professor at Boston University, and a career scientist with Boston’s Department of Veterans Affairs, her NIH and VA-funded research continues to examine brain changes in people with chronic alcohol use disorder.

She then turned to brain damage in people. A professor at Boston University, and a career scientist with Boston’s Department of Veterans Affairs, her NIH and VA-funded research continues to examine brain changes in people with chronic alcohol use disorder.

“I’ve always been fascinated with the way in which the brain controls behavior,” said Berman, director of the neuropsychology lab at Boston University School of Medicine, who delivered NIAAA’s 8th annual Jack Mendelson Honorary Lecture recently. Her foray into understanding alcohol’s effects on the brain began with patients who had Korsakoff’s syndrome, a memory disorder commonly caused by long-standing alcohol misuse.

Korsakoff patients had severe short-term memory loss but excellent memory for events that occurred before their brain damage, explained Berman, and they also would repeatedly tell the same stories.

“I was struck by the repetitious behaviors of Korsakoff patients in the wards,” she said, “and together with their memory impairment, I realized there were certain similarities in the behaviors of the patients and the monkeys I’d studied as a student.” The monkeys with bilateral frontal lobe lesions also had a short-term memory impairment on performance tasks and walked around in circles incessantly.

In earlier research, before the advent of neuroimaging technologies, her lab conducted performance tests to observe behavioral abnormalities beyond amnesia in Korsakoff patients.

“By comparing behavioral deficits in humans to well-documented deficits in monkeys with known damage to a specific brain region, we could infer whether patients had similar damage and dysfunction,” said Berman, employing an approach called comparative neuropsychology.

On basic memory and perception tasks, Korsakoff patients performed worse than both healthy control subjects and uncomplicated alcoholics (who didn’t have Korsakoff syndrome, all of whom had abstained for a month or more). For one test in which patients had to choose the correct colors or sounds to get a reward, the Korsakoff patients needed much more time and made more errors.

“We were able not only to quantify clear indications of prefrontal cortical damage, such as short-term memory deficits and abnormal perseverative behavior in alcoholic Korsakoff patients,” said Berman, “we also showed they had reduced perceptual processing abilities and, in later experiments, we observed deficits in attention, problem-solving difficulties, lower arousal levels and reduced sensitivity to the effects of rewards.”

Korsakoff patients’ brain damage causes impairments beyond short-term memory loss and repetitive responses. Berman’s studies showed their brain damage was more extensive than in uncomplicated alcoholics. They also showed deficits on every emotional function test, including tests using such visual and auditory cues as identifying emotion on faces or the inflection of a voice. Recent functional MRI studies have confirmed widespread cortical atrophy and other brain damage in Korsakoff patients.

“Importantly, we saw alcoholics without the severe impairments characteristic of Korsakoff patients who nonetheless did have perceptual, cognitive and inhibitory deficits compared to nonalcoholic controls,” Berman said. The activation levels of the amygdala (emotion) and hippocampus (memory) were significantly blunted in the long-term alcoholic patients.

Berman discusses the brain damage caused by long-standing alcohol misuse.
Berman discusses the brain damage caused by long-standing alcohol abuse.
PHOTOS: ERNIE BRANSON

Interestingly, when patients had to pace their responses at time intervals, the uncomplicated alcoholics responded well early on but showed abnormal perseverative behavior later in the exercise.

Berman said some experts have posited that alcoholism may modify brain structure without killing neurons, which begs the question of whether neuron repair could occur with sustained abstinence. Her lab has seen evidence of the brain’s resilience and flexibility among the alcoholic group. The prefrontal brain regions may at times use alternative networks while performing cognitive tasks to compensate for decreased processing by other parts of the brain.

“Alcoholism likely affects selective brain systems, leaving other regions relatively intact,” Berman said. “The intact regions then can serve as substitute places in the brain for reassigning functions of the affected areas.”

There were also differences between men and women. Berman’s ongoing studies are showing alcoholic men to have a thinner cerebral cortex and less cerebral white and grey matter volume than the alcoholic women, said Berman. In men, the severity of damage directly correlated to the duration of heavy drinking but in alcoholic women, only a couple of brain regions were affected by duration of drinking.

When examining the size of the extended reward and oversight system (EROS), one large study showed the total EROS was significantly less in alcoholic men than women, particularly in the dorsolateral prefrontal cortex, which controls executive function.

“There’s more and more converging evidence showing not only that alcohol use disorders reflect a damaged brain,” said Berman, “but also that the clinical and functional appearance associated with alcoholism—such as loss of self-control, repetition of compulsive and impulsive behaviors and disinhibition—are tied to an accumulation of abnormalities in multiple interconnected brain systems and at multiple levels of the nervous system.”

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